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Identification and functional analysis of RNA binding proteins associated with the development of glioblastoma multiform

Grant number: 13/25483-4
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): April 01, 2014
Effective date (End): March 31, 2015
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal researcher:Pedro Alexandre Favoretto Galante
Grantee:Bruna Renata Silva Corrêa
Supervisor abroad: Luiz Otavio Ferraz Penalva
Home Institution: Hospital Sírio-Libanês. Sociedade Beneficente de Senhoras (SBSHSL). São Paulo , SP, Brazil
Research place: University of Texas Health Science Center at San Antonio (UTHSCSA), United States  
Associated to the scholarship:13/07159-5 - RNA-binding proteins and post-transcriptional variations: influence on glioblastoma multiforme development, BP.DR


Glioblastoma multiforme (GBM) is one of the most aggressive tumor types, with a median survival time of 15 months. Poor survival is explained by the fact that current treatments are not able to prevent tumor recurrence. Understanding basic aspects of GBM biology, such as its origin, development and resistance is crucial to develop more effective therapies. RNA binding proteins (RBPs) are among the molecules involved in the genesis and development of the GBM. RBPs are critical post-transcriptional gene expression regulators which are implicated in several cellular processes, like mRNA and miRNA processing, stability, degradation, polyadenylation, translation and splice site selection. Changes in their expression levels cause severe alterations in the cellular proteome, which may lead to diseases states and tumorigenesis. Here, we aim to identify RPBs related to the development and resistance of GBM. First, we will select those RBPs by screening gene expression databanks; next, in collaboration with Dr. Penalva's group, we will determine the impact of identified up regulated RBPs in proliferation, invasion, apoptosis and stem cell survival. mRNA targets of the three RBPs showing the most prominent impact on cancer related functions will be determined by the iCLIP approach; their relevance to GBM development will be revealed via bioinformatics studies that will map target genes to biological processes and pathways. In conclusion, we expected that the investigation of central elements that control post-transcriptional regulation in tumor cells, like RBPs, could unveil unknown aspects of GBM development and lead to new possibilities of therapies. (AU)

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Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CORREA, BRUNA R. S.; HU, JOANNA; PENALVA, LUIZ O. F.; SCHLEGEL, RICHARD; RIMM, DAVID L.; GALANTE, PEDRO A. F.; AGARWAL, SEEMA. Patient-derived conditionally reprogrammed cells maintain intra-tumor genetic heterogeneity. SCIENTIFIC REPORTS, v. 8, . (13/07159-5, 13/25483-4)
SANTOS, MARCIA C. T.; TEGGE, ALLISON N.; CORREA, BRUNA R.; MAHESULA, SWETHA; KOHNKE, LUANA Q.; QIAO, MEI; FERREIRA, MARCO A. R.; KOKOVAY, ERZSEBET; PENALVA, LUIZ O. F.. miR-124,-128, and-137 Orchestrate Neural Differentiation by Acting on Overlapping Gene Sets Containing a Highly Connected Transcription Factor Network. Stem Cells, v. 34, n. 1, p. 220-232, . (12/22950-8, 13/25483-4, 11/51588-2)
VELASCO, MITZLI X.; KOSTI, ADAM; GUARDIA, GABRIELA D. A.; SANTOS, MARCIA C.; TEGGE, ALLISON; QIAO, MEI; CORREA, BRUNA R. S.; HERNANDEZ, GRECO; KOKOVAY, ERZSEBET; GALANTE, PEDRO A. F.; et al. Antagonism between the RNA-binding protein Musashi1 and miR-137 and its potential impact on neurogenesis and glioblastoma development. RNA, v. 25, n. 7, p. 768-782, . (13/07159-5, 17/19541-2, 13/25483-4)
GUARDIA, GABRIELA D. A.; CORREA, BRUNA R.; ARAUJO, PATRICIA ROSA; QIAO, MEI; BURNS, SUZANNE; PENALVA, LUIZ O. F.; GALANTE, PEDRO A. F.. Proneural and mesenchymal glioma stem cells display major differences in splicing and lncRNA profiles. NPJ GENOMIC MEDICINE, v. 5, n. 1, . (18/15579-8, 13/07159-5, 17/19541-2, 13/25483-4)
CORREA, BRUNA R.; DE ARAUJO, PATRICIA ROSA; QIAO, MEI; BURNS, SUZANNE C.; CHEN, CHEN; SCHLEGEL, RICHARD; AGARWAL, SEEMA; GALANTE, PEDRO A. F.; PENALVA, LUIZ O. F.. Functional genomics analyses of RNA-binding proteins reveal the splicing regulator SNRPB as an oncogenic candidate in glioblastoma. Genome Biology, v. 17, . (13/07159-5, 13/25483-4)
RAMOS CIRILO, PRISCILA DANIELE; DE SOUSA ANDRADE, LUCIANA NOGUEIRA; SILVA CORREA, BRUNA RENATA; QIAO, MEI; FURUYA, TATIANE KATSUE; CHAMMAS, ROGER; FERRAZ PENALVA, LUIZ OTAVIO. MicroRNA-195 acts as an anti-proliferative miRNA in human melanoma cells by targeting Prohibitin 1. BMC CANCER, v. 17, . (98/14247-6, 13/25483-4, 13/11721-0)

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